USE OF COMBINATION OF ANTI-ANGIOGENIC SUBSTANCE AND c-kit KINASE INHIBITOR

ABSTRACT

The object of the present invention is to find a pharmaceutical composition and a method for treating cancer that show an excellent antitumor effect. Combinational use of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide and analogues thereof can result in an excellent antitumor effect when combined with a substance having a c-kit kinase-inhibiting activity.

FIELD OF THE INVENTION

The present invention relates to a pharmaceutical composition and a kitcomprising a combination of a compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof(hereinafter, also referred to as a “compound of the invention”) and asubstance having a c-kit kinase-inhibiting activity (hereinafter, alsoreferred to as a “c-kit inhibitor”), to a method for treating cancercomprising administering an effective amount of the pharmaceuticalcomposition to a patient, to use of the compound of the invention forproducing the pharmaceutical composition, and to the compound of theinvention used for the pharmaceutical composition.

BACKGROUND OF THE INVENTION

Examples of conventionally used chemotherapeutic agents for cancerinclude alkylating agents such as cyclophosphamide, antimetabolites suchas methotrexate and fluorouracil, antibiotics such as adriamycin,mitomycin and bleomycin, plant-derived taxol, vincristine and etoposideand metal complexes such as cisplatin. None of them, however, providessufficient antitumor effect, and thus development of a novel antitumordrug has been strongly desired.

Recently,4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide(hereinafter, also referred to as “imatinib” or “STI571”) is known as ac-kit inhibitor (Documents 1 and 2).

In addition,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideis known as a VEGF receptor kinase inhibitor (Document 3-4).

However, it has not been elucidated yet what kind of antitumor effectcan or cannot be obtained with a pharmaceutical composition containing acombination of these substances.

DOCUMENTS

-   1. Blood., 96, 925-932, 2000.-   2. J Clin Oncol., 20, 1692-1703, 2002.-   3. International publication No. 02/32872 pamphlet)-   4. International publication No. 2005/063713 (pamphlet)

DISCLOSURE OF THE INVENTION

The present invention was achieved regarding the circumstances describedabove. The problem to be solved by the invention is to find apharmaceutical composition having an excellent antitumor effect and amethod for treating cancer.

In order to solve the above problem, the present inventors have gonethrough keen examination, as a result of which combined use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand c-kit inhibitor imatinib was found to show an excellent antitumoreffect.

Thus, the present invention relates to:

(1) a pharmaceutical composition comprising a combination of a compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof and a substance having a c-kit kinase-inhibitingactivity.

(2) A kit comprising: (a) at least one selected from the groupconsisting of a package, an instruction and an attached documentdescribing combined use of a compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof and asubstance having a c-kit kinase-inhibiting activity; and (b) apharmaceutical composition comprising a compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof.

(3) A kit comprising a set of a formulation containing a compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof, and a formulation containing a substance having ac-kit kinase-inhibiting activity.

(4) A pharmaceutical composition comprising a compound represented byFormula (I), a pharmacologically acceptable salt thereof or a solvatethereof which is administered to a patient with a substance having ac-kit kinase-inhibiting activity.

(5) A method for treating cancer comprising administering an effectiveamount of a compound represented by Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof and an effective amount ofa substance having a c-kit kinase-inhibiting activity to a patient.

(6) Use of a compound represented by Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof for producing apharmaceutical composition in combination with a substance having ac-kit kinase-inhibiting activity.

(7) A compound represented by Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof used for a pharmaceuticalcomposition in combination with a substance having a c-kitkinase-inhibiting activity.

The compound represented by Formula (I), a pharmacologically acceptablesalt thereof or a solvate thereof is as follows:

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent);R² represents cyano group, C₁₋₆ alkoxy group that may have asubstituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent);Y¹ represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent);W¹ and W² each independently represent a carbon atom or a nitrogen atomthat may have a substituent);R³ and R⁴ each independently represent a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent, C₂₋₆ alkenyl group that may have asubstituent, C₂₋₆ alkynyl group that may have a substituent, C₃₋₈cycloalkyl group that may have a substituent, C₂₋₇ acyl group that mayhave a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent;R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent].

Furthermore, the present invention preferably relates to the followings.

(1) A pharmaceutical composition comprising a combination of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof andimatinib.

(2) A kit comprising: (a) at least one selected from the groupconsisting of a package, an instruction and an attached documentdescribing combined use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof andimatinib; and (b) a pharmaceutical composition comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.

(3) A kit comprising a set of a formulation containing4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof and aformulation containing imatinib.

(4) A pharmaceutical composition comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof whichis administered to a patient together with imatinib.

(5) A method for treating cancer comprising administering an effectiveamount of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof and aneffective amount of imatinib to a patient.

(6) Use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof forproducing a pharmaceutical composition in combination with imatinib.

(7)4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof forproducing a pharmaceutical composition in combination with imatinib.

According to the present invention, a pharmaceutical compositioncomprising a combination of a compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof and ac-kit inhibitor is provided, which can be used for treating cancer.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows the combined effect of a VEGF receptor kinase inhibitor anda c-kit inhibitor in a human cancer cell line subcutaneous xenograftmodel. In FIG. 1, Compound A refers to4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand Compound B refers to imatinib.

FIG. 2 shows the combined effect of a VEGF receptor kinase inhibitor anda c-kit inhibitor in a human cancer cell line subcutaneous xenograftmodel. In FIG. 2. Compound A refers to4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand Compound B refers to imatinib.

BEST MODES FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described. Thefollowing embodiments illustrate the present invention, which are notintended to limit the present invention. The present invention may becarried out in various embodiments without departing from the scope ofthe invention.

The documents, laid-open patent applications, patent publications andother patent documents cited herein are incorporated herein byreference. The present specification incorporates the content ofspecification of Japanese Patent Application No. 2005-322946 based onwhich the present application claims priority.

1. Compound

Herein, “a halogen atom” refers to a fluorine atom, a chlorine atom, abromine atom or an iodine atom.

Preferable examples of “a halogen atom” include a fluorine atom and achlorine atom.

Herein, “C₁₋₆ alkyl group” refers to linear or branched alkyl group witha carbon number of 1-6, and specific examples include methyl group,ethyl group, 1-propyl group (n-propyl group), 2-propyl group (i-propylgroup), 2-methyl-1-propyl group (i-butyl group), 2-methyl-2-propyl group(t-butyl group), 1-butyl group (n-butyl group), 2-butyl group (s-butylgroup), 1-pentyl group, 2-pentyl group, 3-pentyl group, 2-methyl-1-butylgroup, 3-methyl-1-butyl group, 2-methyl-2-butyl group, 3-methyl-2-butylgroup, 2,2-dimethyl-1-propyl group, 1-hexyl group, 2-hexyl group,3-hexyl group, 2-methyl-1-pentyl group, 3-methyl-1-pentyl group,4-methyl-1-pentyl group, 2-methyl-2-pentyl group, 3-methyl-2-pentylgroup, 4-methyl-2-pentyl group, 2-methyl-3-pentyl group,3-methyl-3-pentyl group, 2,3-dimethyl-1-butyl group,3,3-dimethyl-1-butyl group, 2,2-dimethyl-1-butyl group, 2-ethyl-1-butylgroup, 3,3-dimethyl-2-butyl group and 2,3-dimethyl-2-butyl group.

Preferable examples of “C₁₋₆ alkyl group” include methyl group, ethylgroup, 1-propyl group, 2-propyl group, 2-methyl-1-propyl group,2-methyl-2-propyl group, 1-butyl group and 2-butyl group.

Herein, “C₁₋₆ alkylene group” refers to divalent group derived from the“C₁₋₆ alkyl group” defined above by removing any one hydrogen atomtherefrom, and specific examples include methylene group, 1,2-ethylenegroup, 1,1-ethylene group, 1,3-propylene group, tetramethylene group,pentamethylene group and hexamethylene group.

Herein, “C₂₋₆ alkenyl group” refers to linear or branched alkenyl grouphaving one double bond and a carbon number of 2-6, and specific examplesinclude ethenyl group (vinyl group), 1-propenyl group, 2-propenyl group(allyl group), 1-butenyl group, 2-butenyl group, 3-butenyl group,pentenyl group and hexenyl group.

Herein, “C₂₋₆ alkynyl group” refers to linear or branched alkynyl grouphaving one triple bond and a carbon number of 2-6, and specific examplesinclude ethinyl group, 1-propynyl group, 2-propynyl group, 1-butynylgroup, 2-butynyl group, 3-butynyl group, pentynyl group and hexynylgroup.

Herein, “C₃₋₈ cycloalkyl group” refers to monocyclic or bicyclicsaturated aliphatic hydrocarbon group with a carbon number of 3-8, andspecific examples include cyclopropyl group, cyclobutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctylgroup, bicyclo[2.1.0]pentyl group, bicyclo[3.1.0]hexyl group,bicyclo[2.1.1]hexyl group, bicyclo[4.1.0]heptyl group,bicyclo[2.2.1]heptyl group (norbornyl group), bicyclo[3.3.0]octyl group,bicyclo[3.2.1]octyl group and bicyclo[2.2.2]octyl group.

Preferable examples of “C₃₋₈ cycloalkyl group” include cyclopropylgroup, cyclobutyl group and cyclopentyl group.

Herein, “C₆₋₁₀ aryl group” refers to aromatic hydrocarbon cyclic groupwith a carbon number of 6-10, and specific examples include phenylgroup, 1-naphthyl group, 2-naphthyl group, indenyl group and azulenylgroup.

A preferable example of “C₆₋₁₀ aryl group” includes phenyl group.

Herein, “a heteroatom” refers to a nitrogen atom, an oxygen atom or asulfur atom.

Herein. “5-10-membered heteroaryl group” refers to aromatic cyclic grouphaving 5-10 atoms forming the ring and 1-5 heteroatoms included in theatom forming the ring, and specific examples include furyl group,thienyl group, pyrrolyl group, imidazolyl group, triazolyl group,tetrazolyl group, thiazolyl group, pyrazolyl group, oxazolyl group,isoxazolyl group, isothiazolyl group, furazanyl group, thiadiazolylgroup, oxadiazolyl group, pyridyl group, pyrazinyl group, pyridazinylgroup, pyrimidinyl group, triazinyl group, purinyl group, pteridinylgroup, quinolyl group, isoquinolyl group, naphthridinyl group,quinoxalinyl group, cinnolinyl group, quinazolinyl group, phthalazinylgroup, imidazopyridyl group, imidazothiazolyl group, imidazoxazolylgroup, benzothiazolyl group, benzoxazolyl group, benzimidazolyl group,indolyl group, isoindolyl group, indazolyl group, pyrrolopyridyl group,thienopyridyl group, furopyridyl group, benzothiadiazolyl group,benzoxadiazolyl group, pyridopyrimidinyl group, benzofuryl group,benzothienyl group and thienofuryl group.

Preferable examples of “5-10-membered heteroaryl group” include furylgroup, thienyl group, pyrrolyl group, imidazolyl group, thiazolyl group,pyrazolyl group, oxazolyl group, isoxazolyl group, isothiazolyl group,pyridyl group and pyrimidinyl group.

Herein, “3-10-membered nonaromatic heterocyclic group”:

(1) has 3-10 atoms forming the ring;

(2) has 1-2 heteroatoms included in the atoms forming the ring;

(3) may include 1-2 double bonds in the ring;

(4) may have 1-3 carbonyl group, sulfinyl group or sulfonyl group in thering; and

(5) is nonaromatic monocyclic or bicyclic group. When a nitrogen atom isincluded in the atoms forming the ring, the nitrogen atom may have abinding hand. Specific examples include aziridinyl group, azetidinylgroup, pyrrolidinyl group, piperidinyl group, azepanyl group, azocanylgroup, piperazinyl group, diazepanyl group, diazocanyl group,diazabicyclo[2.2.1]heptyl group, morpholinyl group, thiomorpholinylgroup, 1,1-dioxothiomorpholinyl group, oxiranyl group, oxetanyl group,tetrahydrofuryl group, dioxoranyl group, tetrahydropyranyl group,dioxanyl group, tetrahydrothienyl group, tetrahydrothiopyranyl group,oxazolidinyl group and thiazolidinyl group.

Preferable examples of “3-10-membered nonaromatic heterocyclic group”include aziridinyl group, azetidinyl group, pyrrolidinyl group,piperidinyl group, azepanyl group, piperazinyl group, diazepanyl group,morpholinyl group, thiomorpholinyl group, 1,1-dioxothiomorpholinylgroup, tetrahydrofuryl group and tetrahydropyranyl group.

Herein, “C₁₋₆ alkoxy group” refers to group in which an oxygen atom isbound to the terminal of “C₁₋₆ alkyl group” defined above, and specificexamples include methoxy group, ethoxy group, 1-propoxy group (n-propoxygroup), 2-propoxy group (i-propoxy group), 2-methyl-1-propoxy group(i-butoxy group), 2-methyl-2-propoxy group (t-butoxy group), 1-butoxygroup (n-butoxy group), 2-butoxy group (s-butoxy group), 1-pentyloxygroup, 2-pentyloxy group, 3-pentyloxy group, 2-methyl-1-butoxy group,3-methyl-1-butoxy group, 2-methyl-2-butoxy group, 3-methyl-2-butoxygroup, 2,2-dimethyl-1-propoxy group, 1-hexyloxy group, 2-hexyloxy group,3-hexyloxy group, 2-methyl-1-pentyloxy group, 3-methyl-1-pentyloxygroup, 4-methyl-1-pentyloxy group, 2-methyl-2-pentyloxy group,3-methyl-2-pentyloxy group, 4-methyl-2-pentyloxy group,2-methyl-3-pentyloxy group, 3-methyl-3-pentyloxy group,2,3-dimethyl-1-butoxy group, 3,3-dimethyl-1-butoxy group,2,2-dimethyl-1-butoxy group, 2-ethyl-1-butoxy group,3,3-dimethyl-2-butoxy group and 2,3-dimethyl-2-butoxy group.

Preferable examples of “C₁₋₆ alkoxy group” include methoxy group, ethoxygroup, 1-propoxy group, 2-propoxy group, 2-methyl-1-propoxy group,2-methyl-2-propoxy group, 1-butoxy group and 2-butoxy group.

Herein, “C₁₋₆ alkylthio group” refers to group in which a sulfur atom isbound to the terminal of “C₁₋₆ alkyl group” defined above, and specificexamples include methylthio group, ethylthio group, 1-propylthio group(n-propylthio group), 2-propylthio group (i-propylthio group),2-methyl-1-propylthio group (i-butylthio group), 2-methyl-2-propylthiogroup (t-butylthio group), 1-butylthio group (n-butylthio group),2-butylthio group (s-butylthio group), 1-pentylthio group, 2-pentylthiogroup, 3-pentylthio group, 2-methyl-1-butylthio group,3-methyl-1-butylthio group, 2-methyl-2-butylthio group,3-methyl-2-butylthio group, 2,2-dimethyl-1-propylthio group, 1-hexylthiogroup, 2-hexylthio group, 3-hexylthio group, 2-methyl-1-pentylthiogroup, 3-methyl-1-pentylthio group, 4-methyl-1-pentylthio group,2-methyl-2-pentylthio group, 3-methyl-2-pentylthio group,4-methyl-2-pentylthio group, 2-methyl-3-pentylthio group,3-methyl-3-pentylthio group, 2,3-dimethyl-1-butylthio group,3,3-dimethyl-1-butylthio group, 2,2-dimethyl-1-butylthio group,2-ethyl-1-butylthio group, 3,3-dimethyl-2-butylthio group and2,3-dimethyl-2-butylthio group.

Preferable examples of “C₁₋₆ alkylthio group” include methylthio group,ethylthio group, 1-propylthio group (n-propylthio group), 2-propylthiogroup (i-propylthio group), 2-methyl-1-propylthio group (i-butylthiogroup), 2-methyl-2-propylthio group (t-butylthio group), 1-butylthiogroup (n-butylthio group) and 2-butylthio group (s-butylthio group).

Herein, “C₃₋₈ cycloalkoxy group” refers to group in which an oxygen atomis bound to the terminal of “C₃₋₈ cycloalkyl group” defined above, andspecific examples include cyclopropoxy group, cyclobutoxy group,cyclopentyloxy group, cyclohexyloxy group, cycloheptyloxy group,cyclooctyloxy group, bicyclo[2.1.0]pentyloxy group,bicyclo[3.1.0]hexyloxy group, bicyclo[2.1.1]hexyloxy group,bicyclo[4.1.0]heptyloxy group, bicyclo[2.2.1]heptyloxy group(norbornyloxy group), bicyclo[3.3.0]octyloxy group,bicyclo[3.2.1]octyloxy group and bicyclo[2.2.2]octyloxy group.

Preferable examples of “C₃₋₈ cycloalkoxy group” include cyclopropoxygroup, cyclobutoxy group and cyclopentyloxy group.

Herein, “mono-C₁₋₆ alkylamino group” refers to group in which a hydrogenatom in amino group is substituted with “C₁₋₆ alkyl group” definedabove, and specific examples include methylamino group, ethylaminogroup, 1-propylamino group (n-propylamino group), 2-propylamino group(i-propylamino group), 2-methyl-1-propylamino group (i-butylaminogroup), 2-methyl-2-propylamino group (t-butylamino group), 1-butylaminogroup (n-butylamino group), 2-butylamino group (s-butylamino group),1-pentylamino group, 2-pentylamino group, 3-pentylamino group,2-methyl-1-butylamino group, 3-methyl-1-butylamino group,2-methyl-2-butylamino group, 3-methyl-2-butylamino group,2,2-dimethyl-1-propylamino group, 1-hexylamino group, 2-hexylaminogroup, 3-hexylamino group, 2-methyl-1-pentylamino group,3-methyl-1-pentylamino group, 4-methyl-1-pentylamino group,2-methyl-2-pentylamino group, 3-methyl-2-pentylamino group,4-methyl-2-pentylamino group, 2-methyl-3-pentylamino group,3-methyl-3-pentylamino group, 2,3-dimethyl-1-butylamino group,3,3-dimethyl-1-butylamino group, 2,2-dimethyl-1-butylamino group,2-ethyl-1-butylamino group, 3,3-dimethyl-2-butylamino group and2,3-dimethyl-2-butylamino group.

Herein, “di-C₁₋₆ alkylamino group” refers to group in which two hydrogenatoms in amino group are substituted with identical or different “C₁₋₆alkyl group” defined above, and specific examples includeN,N-dimethylamino group, N,N-diethylamino group, N,N-di-n-propylaminogroup, N,N-di-i-propylamino group, N,N-di-n-butylamino group,N,N-di-i-butylamino group, N,N-di-s-butylamino group,N,N-di-t-butylamino group, N-ethyl-N-methylamino group,N-n-propyl-N-methylamino group, N-i-propyl-N-methylamino group,N-n-butyl-N-methylamino group, N-i-butyl-N-methylamino group,N-s-butyl-N-methylamino group and N-t-butyl-N-methylamino group.

Herein, “C₂₋₇ acyl group” refers to carbonyl group bound with “C₁₋₆alkyl group” defined above, and specific examples include acetyl group,propionyl group, isopropionyl group, butyryl group, isobutyryl group,valeryl group, isovaleryl group and pivaloyl group.

Herein, “C₂₋₇ alkoxycarbonyl group” refers to carbonyl group bound with“C₁₋₆ alkoxy group” defined above, and specific examples includemethoxycarbonyl group, ethoxycarbonyl group, 1-propyloxycarbonyl group,2-propyloxycarbonyl group and 2-methyl-2-propoxy group.

Herein, “that may have a substituent” means “that may have one or moresubstituents in any combination at substitutable positions”, andspecific examples include a halogen atom, hydroxyl group, thiol group,nitro group, cyano group, formyl group, carboxyl group, amino group,silyl group, methanesulfonyl group, C₁₋₆ alkyl group, C₂₋₆ alkenylgroup, C₂₋₆ alkynyl group, C₃₋₈ cycloalkyl group, C₆₋₁₀ aryl group,5-10-membered heteroaryl group, 3-10-membered nonaromatic heterocyclicgroup, C₁₋₆ alkoxy group, C₁₋₆ alkylthio group, C₃₋₈ cycloalkoxy group,mono-C₁₋₆ alkylamino group, di-C₁₆ alkylamino group, C₂₋₇ acyl group andC₂₋₇ alkoxycarbonyl group. In this case, C₁₋₆ alkyl group, C₂₋₆ alkenylgroup, C₂₋₆ alkynyl group, C₃₋₈ cycloalkyl group, C₆₋₁₀ aryl group,5-10-membered heteroaryl group, 3-10-membered nonaromatic heterocyclicgroup, C₁₋₆ alkoxy group, C₁₋₆ alkylthio group, C₃₋₈ cycloalkoxy group,mono-C₁₋₆ alkylamino group, di-C₁₋₆ alkylamino group, C₂₋₇ acyl groupand C₂₋₇ alkoxycarbonyl group may each independently have 1-3 groupsselected from the group consisting from the following substituentgroups.

<Substituent Groups>

A halogen atom, hydroxyl group, thiol group, nitro group, cyano group,C₁₋₆ alkyl group, C₃₋₈ cycloalkyl group, C₂₋₆ alkenyl group, C₂₋₆alkynyl group, C₆₋₁₀ aryl group, 5-10-membered heteroaryl group,3-10-membered nonaromatic heterocyclic group, C₁₋₆ alkoxy group and C₁₋₆alkylthio group.

(A) Compound of the Invention

According to the present invention, compound represented by Formula (I)is as follows.

R¹ represents group represented by Formula —V¹—V²—V³ (wherein, V¹represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent).

A preferable example of R¹ includes C₁₋₆ alkyl group. In this case, R¹may have a substituent selected from 3-10-membered nonaromaticheterocyclic group which may have C₁₋₆ alkyl group, hydroxyl group, C₁₋₆alkoxy group, amino group, mono-C₁₋₆ alkylamino group and di-C₁₋₆alkylamino group.

More preferable examples of R¹ include methyl group and grouprepresented by any one of Formulae

(wherein, R^(a3) represents methyl group; R^(a1) represents a hydrogenatom or hydroxyl group; R^(a2) represents methoxy group, ethoxy group,1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group,dimethylamino group or diethylamino group).

Still more preferable examples of R¹ include methyl group and2-methoxyethyl group.

(ii) R²

R² represents cyano group, C₁₋₆ alkoxy group that may have asubstituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent).

Preferable examples of R² include cyano group or group represented byFormula —CONV^(a11)V^(a12) (wherein, V^(a11) and V^(a12) have the samemeaning as defined above).

More preferable examples of R² include cyano group or group representedby Formula —CONHV^(a16) (wherein, V^(a16) represents a hydrogen atom,C₁₋₆ alkyl group, C₃₋₈ cycloalkyl group, C₁₋₆ alkoxy group or C₃₋₈cycloalkoxy group, where V^(a16) may have a substituent selected from ahalogen atom, cyano group, hydroxyl group and C₁₋₆ alkoxy group).

Still more preferable example of R² includes group represented byFormula —CONHV^(a17) (wherein, V^(a17) represents a hydrogen atom, C₁₋₆alkyl group or C₁₋₆ alkoxy group).

The most preferable example of R² include group represented by Formula—CONHV^(a18) (wherein, V^(a18) represents a hydrogen atom, methyl groupor methoxy group).

(iii) Y¹

Y¹ represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); andW¹ and W² each independently represent a carbon atom or a nitrogen atomthat may have a substituent).

A preferable example of Y¹ includes group represented by Formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

(iv) R³ and R⁴

R³ and R⁴ each independently represent a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent, C₂₋₆ alkenyl group that may have asubstituent, C₂₋₆ alkynyl group that may have a substituent, C₃₋₈cycloalkyl group that may have a substituent, C₂₋₇ acyl group that mayhave a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent.

A preferable example of R³ and R⁴ includes a hydrogen atom.

(v) R⁵

R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent.

Preferable examples of R⁵ include a hydrogen atom, C₁₋₆ alkyl group,C₃₋₈ cycloalkyl group and C₆₋₁₀ aryl group (where R⁵ may have asubstituent selected from a halogen atom and methanesulfonyl group).

More preferable examples of R⁵ include methyl group, ethyl group orcyclopropyl group.

Moreover, preferable examples of the compound represented by Formula (I)include:

-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide.-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea.

More preferable examples of the compound represented by Formula (I)further include:

-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide.

A still more preferable example of the compound represented by Formula(I) further includes4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(see Formula (II)).

The most preferable example of the compound represented by Formula (I),a pharmacologically acceptable salt thereof or a solvate thereofincludes methanesulfonate of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.

The compound represented by Formula (I) can be produced by a knownmethod, for example, by methods described in International publicationNo. 02/32872 pamphlet (WO02/32872) and International publication No.2005/063713 pamphlet (WO2005/063713).

(B) C-Kit Inhibitor

According to the present invention, examples of the c-kit inhibitorinclude:

(1)4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide(hereinafter, also referred to as “imatinib” or “STI571”. Blood., 96,925-932, 2000, Bioorganic and Medicinal Chemistry Letters., 7: 187-192,1997) (see Formula (III))

(2) 3-[(2,4-dimethylpyrrole-5-yl)methylene]-2-indolinone (hereinafter,also referred to as “SU5416” or “semaxanib”. Cancer Research., 61,3660-3668, 2000, Journal of Medicinal Chemistry., 41: 2588-2603, 1998,U.S. Pat. No. 5,792,783) (see Formula (IV))

(Z)-3-[(2,4-dimethyl-5-(2-oxo-1,2-dihydroindole-3-ylidenemethyl)-1H-pyrrole-3-yl)-propionicacid (hereinafter, also referred to as “SU6668”. Cancer Research., 61,3660-3668, 2000, Journal of Medicinal Chemistry., 42: 5120-5130, 1999)(see Formula (V))

5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylicacid (2-diethylaminoethyl)amide (hereinafter, also referred to as“SU11248”. Molecular Cancer Therapeutics., 2:471-478, 2003, Journal ofMedicinal Chemistry., 46: 1116-9, 2003) (see Formula (VI))

(5)N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea(hereinafter, also referred to as “KRN633”. Molecular CancerTherapeutics., 3:1639-49, 2004) (see Formula (VII))

(6) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine (hereinafter,also referred to as “PTK787/ZK222584” or “vatalanib”. Cancer Research,60, 2178-2189, 2000, Journal of Medicinal Chemistry., 43:2310-23, 2000,WO98/35958) (see Formula (VIII))

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea(hereinafter, also referred to as “KRN951”. Proceedings of the AmericanAssociation for Cancer Research, 45, 594, (Abstract 2571), 2004,Proceedings of the American Association for Cancer Research, 45, 595,(Abstract 2575), 2004, WO2002/088110) (see Formula (IX))

4-[(4-fluoro-2-methylindole-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidine-1-yl)propoxy]quinazoline(hereinafter, also referred to as “AZD2171”. Cancer Research.65:4389-400, 2005, WO00/47212) (see Formula (X))

(9)6-[2-(methylcarbamoyl)phenylsulfanil]-3-E-[2-(pyridine-2-yl)ethenyl]indazole(hereinafter, also referred to as “AG013736”. Proceedings of theAmerican Association for Cancer Research, 44, 865, (Abstract 3780),2003, American Journal of Pathology. 165:35-52, 2004, WO01/002369) (seeFormula (XI))

N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea(hereinafter, also referred to as “BAY 43-9006” or “sorafenib”. CancerResearch., 64, 7099-7109, 2004, Organic Process Res Dev., 6, 777-81,2002, WO00/42012) (see Formula (XII))

[6-[4-[(4-ethylpiperazine-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yl]-((R)-1-phenylethyl)amine(hereinafter, also referred to as “AEE-788”. Cancer Research., 64,4931-4941, 2004, Cancer Research., 64, 7977-7984, 2004) (see Formula(XIII))

6-(2,6-dichloro-phenyl)-2-(4-fluoro-3-methyl-phenylamino)-8-methyl8H-pyrido[2,3-d]pyrimidine-7-one(hereinafter, also referred to as “PD180970”. Cancer Research., 6,4244-4255, 2002, Journal of Medicinal Chemistry., 40, 2296-2303, 1997)(see Formula (XIV))

6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanilphenylamino)-8H-pyrido[2,3-/d/]pyrimidine-7-one(hereinafter, also referred to as “PD173955”. Cancer Research., 62,4244-4255, 2002, Journal of Medicinal Chemistry., 40, 2296-2303, 1997)(see Formula (XV))

4-[6-methoxy-7-(3-piperidine-1-yl-propoxy)quinazoline-4-yl]piperazine-1-carboxylicacid(4-isopropoxyphenyl)amide (hereinafter, also referred to as “MLN518”or “tandutinib”. Blood., 104, 3754-3757, 2004, Journal of MedicinalChemistry., 45, 3772-3793, 2002) (see Formula (XVI))

N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazine-1-yl]-2-methylpyrimidine-4-yl]amino]thiazole-5-carboxamide(hereinafter, also referred to as “BMS-354825” or “dasatinib”.Proceedings of the National Academy of Sciences of the United States ofAmerica., 102, 11011-11016, 2005) (see Formula (XVII))

Imatinib, SU5416, SU6668, SU11248, KRN633, PTK787/ZK222584, KRN951,AZD2171, AG013736, BAY 43-9006, AEE-788, PD180970, PD173955, MLN518 andBMS-354825 can be produced by a known method, for example, by methodsdescribed in the respective documents.

In addition, imatinib is available by purchasing Glivec™ from NovartisPharma K.K.

According to the present invention, the compound represented by Formula(I) and/or the c-kit inhibitor may form a pharmacologically acceptablesalt with acid or base.

The compound represented by Formula (I) and/or the c-kit inhibitor ofthe invention also comprises such pharmacologically acceptable salts.Examples of salts formed with acid include inorganic acid salts such ashydrochloride, hydrobromate, sulfate and phosphate, and organic acidsalts such as formic acid, acetic acid, lactic acid, succinic acid,fumaric acid, maleic acid, citric acid, tartaric acid, stearic acid,benzoic acid, methanesulfonic acid, benzenesulfonic acid,p-toluenesulfonic acid and trifluoroacetic acid. Examples of saltsformed with base include alkali metal salts such as sodium salt andpotassium salt, alkaline earth metal salts such as calcium salt andmagnesium salt, organic base salts such as trimethylamine,triethylamine, pyridine, picoline, dicyclohexylamine, N,N′-dibenzylethylenediamine, arginine and lysine and ammonium salt.

Furthermore, according to the present invention, the compoundrepresented by Formula (I) and/or the c-kit inhibitor also comprises, ifany, solvates and enantiomers thereof. Examples of solvates includehydrates and nonhydrates, preferably hydrates. Examples of solventsinclude water, alcohols (for example, methanol, ethanol, n-propanol) anddimethylformamide.

Moreover, according to the present invention, the compound representedby Formula (I) may be crystalline or amorphous. If a crystallinepolymorph is present, it may be a single product of any one of thecrystal forms or a mixture of such forms.

According to the present invention, the compound of the invention and/orthe c-kit inhibitor also comprises compounds that generate the compoundrepresented by Formula (I) and/or the c-kit inhibitor by undergoingmetabolism such as oxidation, reduction and hydrolysis in vivo.

According to the present invention, an example of the c-kit inhibitorincludes an anti-c-kit kinase antibody.

According to the present invention, an anti-c-kit kinase antibody is anantibody that has affinity with c-kit kinase or a partial fragmentthereof. Preferably, an anti-c-kit kinase antibody is a neutralizingantibody that recognizes and binds with c-kit kinase to inhibit thevascular endothelial cell growth activity of c-kit kinase. According tothe present invention, an anti-c-kit kinase antibody is, for example, apolyclonal antibody, a monoclonal antibody, a chimeric antibody, asingle-chain antibody (scFV) (Huston et al. (1988) Proc. Natl. Acad.Sci. USA 85: 5879-83; The Pharmacology of Monoclonal Antibody, vol. 113,Rosenburg and Moore ed., Springer Verlag (1994) pp. 269-315), ahumanized antibody, a polyspecific antibody (LeDoussal et al. (1992)Int. J. Cancer Suppl. 7: 58-62; Paulus (1985) Behring Inst. Mitt. 78:118-32; Millstein and Cuello (1983) Nature 305: 537-9; Zimmermann (1986)Rev. Physiol. Biochem. Pharmacol. 105: 176-260; Van Dijk et al. (1989)Int. J. Cancer 43: 944-9), or antibody fragments such as Fab, Fab′,F(ab′)2, Fc and Fv, preferably a monoclonal antibody. Furthermore, ifnecessary, an anti-c-kit kinase antibody may be modified withpolyethyleneglycol (PEG) or the like. Otherwise, an anti-c-kit kinaseantibody may be produced as a fusion protein with β-galactosidase, MBP(maltose binding protein), GST (glutathione S-transferase), GFP (greenfluorescence protein) or the like, which can be detected in an ELISAmethod or the like without using a secondary antibody. An anti-c-kitkinase antibody may be modified by being labeled with biotin or the likesuch that the antibody can be collected using avidin, streptavidin orthe like.

An anti-c-kit kinase antibody may be produced according to aconventional method using c-kit kinase or a partial fragment thereof(hereinafter, also referred to as a “polypeptide fragment of c-kitkinase”), or a cell expressing c-kit kinase or a partial fragmentthereof as a sensitized antigen (“Current Protocols in MolecularBiology” (John Wiley & Sons (1987) Section 11.4-11.13)). In this case, apolypeptide fragment of c-kit kinase may be a fusion protein with an Fcregion, GST, MBP, GFP, AP (alkaline phosphatase) or the like.

A polyclonal antibody and a monoclonal antibody may be preparedaccording to a method known by those skilled in the art (Antibodies: ALaboratory Manual, E. Harlow and D. Lane, ed., Cold Spring HarborLaboratory (Cold Spring Harbor, N.Y., 1988)).

A polyclonal antibody may be obtained, for example, by administering anantigen to a mammal such as a mouse, a rabbit or a rat, collecting bloodfrom this mammal, and separating and purifying an antibody from thecollected blood. Immune sensitization methods are known by those skilledin the art, and may be carried out, for example, by administering anantigen once or more. Furthermore, an antigen (a polypeptide fragment ofc-kit kinase) may be used by dissolving it in an appropriate buffer suchas a buffer containing a complete Freund's adjuvant or a generally usedadjuvant such as aluminum hydroxide, although no adjuvant may be useddepending on the administration route or conditions.

Blood is taken from the mammal 1-2 months after the last immunesensitization, and separated and purified according to a conventionalmethod such as centrifugation, precipitation using ammonium sulfate orpolyethyleneglycol and various chromatographies, thereby obtaining apolyclonal antibody as a polyclonal antiserum.

An example of a method for producing a monoclonal antibody includes ahybridoma technique. The hybridoma technique first sensitizes a mammalin the same manner as in the production of the polyclonal antibody.Preferably, partial blood collection is carried out appropriate daysafter the sensitization to determine the antibody titer by a knownmethod such as ELISA method.

Subsequently, spleen is removed from the sensitized animal to obtain Bcells. Then, the B cells are fused with myeloma cells by a common methodto produce antibody-producing hybridomas. The myeloma cells used are notparticularly limited and known cells may be used. The method for fusingthe cells may be any method selected from methods known in the art suchas Sendai virus technique, polyethyleneglycol technique and protoplasttechnique. The obtained hybridomas are cultured for an appropriateperiod of time in an HAT medium (a medium containing hypoxanthine,aminopterin and thymidine) by a common method for hybridoma selection.Then, the antibody-producing hybridoma of interest may be screened andcloned.

A known antibody detecting method such as ELISA method orradioimmunoassay method may be used as the screening method, and amethod known in the art such as limiting dilution technique, FACS methodor the like may be used as the cloning method. The obtained hybridomamay be cultured in an appropriate culture solution, or may beintraperitoneally administered, for example, to a mouse that iscompatible with the hybridoma. The desired monoclonal antibody can beisolated and purified from the resulting culture solution or ascites bysalt-out, ion-exchange chromatography, gel filtration, affinitychromatography or the like.

2. Pharmaceutical Composition, Kit and Method for Treating Cancer

The present invention relates to a pharmaceutical composition, a kit, amethod for treating cancer or the like characterized by combining acompound of the invention and a c-kit inhibitor.

According to the present invention, the c-kit inhibitor is notparticularly limited as long as it has an activity of inhibiting c-kitkinase. Examples of the c-kit inhibitor include a c-kit kinase inhibitorand an anti-c-kit kinase antibody. Preferable examples of c-kitinhibitors include imatinib, SU5416, SU6668, SU11248, KRN633,PTK787/ZK222584, KRN951, AZD2171, AG013736, BAY 43-9006, AEE-788,PD180970, PD173955, MLN518 and BMS-354825, and more preferable exampleincludes imatinib.

According to the present invention, the phrase “in combination” refersto a combination for combined use of the compound, and includes both aform for concomitantly using separate substances upon administration anda form as a mixture.

The dosage form of the formulation included in the kit of the inventionis not particularly limited as long as it contains the compound of theinvention and/or the c-kit inhibitor. The pharmaceutical compositionand/or the kit of the invention is useful as a pharmaceuticalcomposition and/or a kit for treating cancer.

The pharmaceutical composition and/or the kit of the invention may beused as a drug for treating cancer.

According to the present invention, a drug for treating cancer comprisesan antitumor drug, a drug for improving prognosis of cancer, a drug forpreventing cancer recurrence, a drug for suppressing cancer metastasisand the like.

The effect of cancer treatment may be confirmed by observation of ax-ray picture, CT or the like, by histopathological diagnosis of biopsy,or from a tumor marker value.

The pharmaceutical composition and/or the kit of the invention may beadministered to a mammal (e.g., human, rat, rabbit, sheep, pig, bovine,cat, dog, monkey, etc.).

The types of cancer treated by the drug are not particularly limited andmay include, for example, brain cancer, head&neck cancer, esophaguscancer, tongue cancer, lung cancer, breast cancer, pancreatic cancer,stomach cancer, small intestine cancer, duodenum cancer, colorectalcancer (colon cancer, rectal cancer), bladder cancer, kidney cancer,liver cancer, prostate cancer, uterus cancer, ovary cancer, thyroidgland cancer, gallbladder cancer, pharynx cancer, sarcoma (e.g.,osteosarcoma, chondrosarcoma, Kaposi's sarcoma, myosarcoma,angiosarcoma, fibrosarcoma, etc.), leukemia (e.g., chronic myeloidleukemia (CML), acute myeloid leukemia (AML), chronic lymphatic leukemia(CLL) and acute lymphatic leukemia (ALL), lymphoma, multiple myeloma(MM), etc.) and melanoma.

The pharmaceutical composition and/or the kit of the invention may beused through oral or parental administration. When the pharmaceuticalcomposition and/or the kit of the invention is used, the given dose ofthe compound of the invention differs depending on the degree of thesymptom, age, sex, weight and sensitivity difference of the patient,administration mode, administration period, administration interval,nature, prescription and the type of the pharmaceutical formulation, andthe type of the active element. Usually, but without limitation, thedose of the compound is 0.1-1000 mg/day, preferably 0.5-100 mg/day, morepreferably 1-30 mg/day for an adult (weight 60 kg), which may beadministered once to three times a day.

When the pharmaceutical composition and/or kit of the invention is used,the given dose of the c-kit inhibitor is usually, but withoutlimitation, 10-6000 mg/day, preferably 50-4000 mg/day, more preferably50-2000 mg/day for an adult, which may be administered once to threetimes a day.

In addition, when the pharmaceutical composition and/or the kit of theinvention is used, the given dose of the c-kit kinase inhibitor isusually, but without limitation, 10-6000 mg/day, preferably 50-4000mg/day, more preferably 50-2000 mg/day for an adult, which may beadministered once to three times a day.

When the pharmaceutical composition and/or the kit of the invention isused, the given dose of an anti-c-kit kinase antibody is usually, butwithout limitation, 1-6000 mg/day, preferably 10-2000 mg/day, morepreferably 10-1000 mg/day for an adult, which may be administered once aday or a week.

The amount of the compound of the invention used is not particularlylimited and may differ according to the individual combination with thec-kit inhibitor, for example, it may be about 0.01-100 times (weightratio) the amount of the c-kit inhibitor. More preferably, it is about0.1-10 times (weight ratio) the amount of the c-kit inhibitor.

The pharmaceutical composition of the invention may be made into variousforms, for example, into solid oral formulations, injectable solution orthe like.

Furthermore, each of the compound and the c-kit inhibitor contained inthe kit of the invention may individually be made into solid oralformulations, injectable solution or the like.

In order to prepare a solid oral formulation, an excipient, and ifnecessary, a binder, disintegrant, lubricant, colorant, a flavoringagent and the like are added to the principal agent, and then made intoa tablet, a coated tablet, granule, fine granule, dispersant, a capsuleor the like according to a conventional method.

For example, lactose, cornstarch, sucrose, glucose, sorbit, crystallinecellulose, silicon dioxide or the like may be used as the excipient; forexample, polyvinyl alcohol, ethyl cellulose, methyl cellulose, gumarabic, hydroxypropyl cellulose, hydroxypropylmethyl cellulose or thelike may be used as the binder; for example, magnesium stearate, talc,silica or the like may be used as the lubricant; those that are allowedto be added to drugs may be used as the colorant; and for example, cocoapowder, menthol, aromatic acid, peppermint oil, camphor, cinnamon powderor the like may be used as the flavoring agent. Of course, if necessary,these tablets and granule may be coated appropriately with sugarcoating, gelatin coating or else.

When an injectable solution is to be prepared, if necessary, theprincipal agent may be added with a pH adjuster, a buffer, a suspendingagent, a solubilizing agent, a stabilizer, a tonicity agent, apreservative or the like, and may be made into an intravenously,subcutaneously or intramuscularly injectable solution according to aconventional method. If necessary, the solution may be made into alyophilized form by a conventional technique.

Examples of the suspending agent include methyl cellulose, Polysorbate80, hydroxyethyl cellulose, gum arabic, powdered tragacanth, carboxymethyl cellulose sodium and polyoxyethylene sorbitan monolaurate.

Examples of the solubilizing agent include polyoxyethylene hydrogenatedcastor oil, Polysorbate 80, nicotine acid amide, polyoxyethylenesorbitan monolaurate, macrogol, and castor oil fatty acid ethyl ester.

Examples of the stabilizer include sodium sulfite and sodiummetasulfite; examples of the preservative include methylparahydroxybenzoate, ethyl parahydroxybenzoate, sorbic acid, phenol,cresol and chlorocresol.

In the kit of the invention, a formulation containing the compound ofthe invention and a formulation containing the c-kit inhibitor may bemixed together or may be separately accommodated and packed together.The order of the formulations above is not particularly limited and theymay be administered simultaneously or one may be administered after theother.

Besides the compound of the invention and the c-kit inhibitor, thepharmaceutical composition and/or the kit of the invention may alsocontain a package, an instruction, an attached document or the like. Thepackage, the instruction, the attached document or the like may includedescription of a combination employed for using substances, anddescription of usage and dosage in the case of administering separatesubstances in combination or in the case of administering them in a formof a mixture. The usage and dosage may be described referring to therelated description above.

The kit of the invention may also comprise: (a) at least one selectedfrom the group consisting of a package, an instruction and an attacheddocument describing combined use of the compound of the invention andthe c-kit inhibitor; and (b) a pharmaceutical composition containing thecompound of the invention. The kit is useful for treating cancer. Thepharmaceutical composition containing the compound of the invention isuseful for treating cancer. The package, the instruction, the attacheddocument or the like may include the description of combined use of thecompound, and description of usage and dosage in the case ofadministering separate substances in combination upon administration orin the case of administering them in the form of a mixture. The usageand dosage may be described referring to the description ofpharmaceutical composition and kit above.

The present invention also comprises use of a compound of the inventionfor producing a pharmaceutical composition in combination with a c-kitinhibitor. According to the use of the invention, the pharmaceuticalcomposition is useful for treating cancer.

The present invention also comprises a method for preventing or treatingcancer comprising simultaneously or separately administering a compoundof the invention and a c-kit inhibitor to a patient. According to themethod of the invention for preventing or treating cancer, the route andthe method for administering the compound of the invention and the c-kitinhibitor are not particularly limited and reference may be made to thedescription of the pharmaceutical composition of the invention above.

The present invention also comprises a pharmaceutical compositioncontaining the compound of the invention which is simultaneously orseparately administered with a c-kit inhibitor to a patient. For thepharmaceutical composition of the invention, the route and the methodfor administering the compound of the invention and the c-kit inhibitorare not particularly limited and reference may be made to thedescription of the pharmaceutical composition of the invention above.

EXAMPLES

Hereinafter, the present invention will be illustrated by way ofspecific examples, although the invention should not be limited thereto.

Example 1 Combinational Use of Compound of the Invention and c-KitInhibitor in Human Cancer Cell Line Subcutaneous Xenograft Model (InVivo)

Human gastrointestinal stromal tumor cell line GIST882 (supplied by TheBrigham and Women's Hospital, Inc.) was cultured in RPMI1640 (containing10% FBS) in a 5% carbon dioxide incubator to about 80% confluence.Following cultivation, each cell was collected by trypsin-EDTA treatmentaccording to a general method. Using a phosphate buffer containing 50%matrigel, 5×10⁷ cells/mL suspension was prepared, and 0.2 mL each of theresulting cell suspension was subcutaneously transplanted into the flankof a nude mouse. Starting from twenty-one days after thetransplantation,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(10 mg/kg or 30 mg/kg, once a day, for two weeks) and imatinib (160mg/kg, twice a day, for two weeks) were orally administered alone or incombination.4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(methanesulfonate)was prepared based on the description of International publication No.02/32872 pamphlet (WO02/32872). Moreover, imatinib was purchased fromNovartis Pharma K.K. The major and minor axes of tumors were measuredwith Digimatic caliper (Mitsutoyo), and tumor volumes and relative tumorvolumes were calculated according to the following formulae.

Tumor Volume (TV)=Major axis of tumor (mm)×(Minor axis of tumor)²(mm²)/2

Relative Tumor Volume (RTV)=Tumor volume on measurement day/Tumor volumeon the first administration day

As a result, combined use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand imatinib showed greater antitumor effect than the case where4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideor imatinib was used alone (Tables 1 and 2, FIGS. 1 and 2). Furthermore,combined use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand imatinib showed greater antitumor effect than the case whereimatinib was used alone (Tables 1 and 2, FIGS. 1 and 2).

TABLE 1 Relative tumor volume on Day 15 Administered compound Average ±standard deviation Control (untreated) 2.71 ± 0.24 Imatinib 160 mg/kg1.03 ± 0.15 Compound A 10 mg/kg 2.06 ± 0.16 Compound A 10 mg/kg + 0.77 ±0.12 imatinib 160 mg/kg

Table 1 shows antitumor effects obtained with4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(indicated as Compound A in Table 1) alone, imatinib alone and combineduse of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand imatinib in human cancer cell line subcutaneous xenograft models.The first day of administration was considered Day 1.

TABLE 2 Relative tumor volume on Day 15 Administered compound Average ±standard deviation Control (untreated) 2.71 ± 0.24 Imatinib 160 mg/kg1.03 ± 0.15 Compound A 30 mg/kg 1.36 ± 0.13 Compound A 30 mg/kg + 0.62 ±0.09 imatinib 160 mg/kg

Table 2 shows antitumor effects obtained with4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(indicated as Compound A in Table 2) alone, imatinib alone and combineduse of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand imatinib in human cancer cell line subcutaneous xenograft models.The first day of administration was considered Day 1.

From the obtained results, the combination of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand imatinib was found to provide a pharmaceutical composition and a kitthat show a remarkable antitumor activity, which can be used fortreating cancer.

Reference Example

Hereinafter, a method for producing a formulation of one of thecompounds represented by Formula (I),4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamidewill be described as a reference example.

(Production of Pharmaceutical Composition)

(1) 1 mg Tablet

24 g of crystal (C) of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamidemethanesulfonate (hereinafter, also referred to as “crystal (C)”, whichwas produced according to the method described in Example 7 ofWO2005/063713) and 192 g of light anhydrous silicic acid (antigellingagent sold under the trade name of AEROSIL™200, Nippon Aerosil) weremixed with 20 L Super Mixer, and then 1236 g of D-mannitol (excipient,Towa-Kasei), 720 g of crystalline cellulose (excipient sold under thetrade name of Avicel PH101, Asahi Kasei) and 72 g ofhydroxypropylcellulose (binder sold under the trade name of HPC-L.Nippon Soda) were further added and mixed together. Subsequently, asuitable amount of anhydrous ethanol was added to obtain a granulatedbody containing crystal (C). This granulated body was dried in a rackdryer (60° C.), and then size-regulated using PowerMILL to obtaingranules. Together with the granules, 120 g of croscarmellose sodium(disintegrant sold under the trade name of Ac-Di-Sol, FMC InternationalInc.) and 36 g of sodium stearyl fumarate (lubricant, JRS Pharma LP)were placed in a 20 L tumbler mixer and mixed together, and molded witha tablet machine to obtain tablets with a total mass of 100 mg pertablet. Moreover, the tablets were coated with a tablet coating machineusing aqueous 10% Opadry yellow (OPADRY 03F42069 YELLOW, Colorcon Japan)solution as a coating solution, thereby obtaining coated tablets with atotal mass of 105 mg per tablet.

(2) 10 mg Tablet

60 g of crystal (C) and 192 g of light anhydrous silicic acid(antigelling agent sold under the trade name of AEROSIL™200, NipponAerosil) were mixed with 20 L Super Mixer, and then 1200 g of D-mannitol(excipient, Towa-Kasei), 720 g of crystalline cellulose (excipient soldunder the trade name of Avicel PH101, Asahi Kasei) and 72 g ofhydroxypropylcellulose (binder sold under the trade name of HPC-L,Nippon Soda) were further added and mixed together. Subsequently, asuitable amount of anhydrous ethanol was added to obtain a granulatedbody containing crystal (C). This granulated body was dried in a rackdryer (60° C.), and then size-regulated using PowerMILL to obtaingranules. Together with the granules, 120 g of croscarmellose sodium(disintegrant sold under the trade name of Ac-Di-Sol, FMC InternationalInc.) and 36 g of sodium stearyl fumarate (lubricant, JRS Pharma LP)were placed in a 20 L tumbler mixer and mixed together, and molded witha tablet machine to obtain tablets with a total mass of 400 mg pertablet. Moreover, the tablets were coated with a tablet coating machineusing aqueous 10% Opadry yellow (OPADRY 03F42069 YELLOW, Colorcon Japan)solution as a coating solution, thereby obtaining coated tablets with atotal mass of 411 mg per tablet.

(3) 100 mg Tablet

31.4 g of crystal (C) and 4 g of light anhydrous silicic acid(antigelling agent sold under the trade name of AEROSIL™200, NipponAerosil) were mixed with 1 L Super Mixer, and then 40.1 g of anhydrouscalcium hydrogen phosphate (excipient, Kyowa Chemical Industry), 10 g oflow substituted hydroxypropylcellulose (binder sold under the trade nameof L-HPC (LH-21), Shin-Etsu Chemical) and 3 g of hydroxypropylcellulose(binder sold under the trade name of HPC-L, Nippon Soda) were furtheradded and mixed together. Subsequently, a suitable amount of anhydrousethanol was added to obtain a granulated body containing crystal (C).This granulated body was dried in a rack dryer (60° C.), and thengranulated using PowerMILL to obtain granules. Together with thegranules 10 g of croscarmellose sodium (disintegrant sold under thetrade name of Ac-Di-Sol. FMC International Inc.) and 1.5 g of sodiumstearyl fumarate (lubricant, JRS Pharma LP) were mixed and molded with atablet machine to obtain tablets with a total mass of 400 mg per tablet.

INDUSTRIAL APPLICABILITY

According to the present invention, there is provided a pharmaceuticalcomposition and/or kit comprising a combination of a compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof and a c-kit inhibitor, which can be used fortreating cancer.

1. A pharmaceutical composition comprising a combination of a compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof and a substance having a c-kit kinase-inhibitingactivity:

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶SO₂—, (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkylgroup that may have a substituent or C₃₋₈ cycloalkyl group that may havea substituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent); R² represents cyano group, C₁₋₆ alkoxy group that may havea substituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent); Y¹represents Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); W¹ and W² eachindependently represent a carbon atom or a nitrogen atom that may have asubstituent); R³ and R⁴ each independently represent a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₄ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₂₋₇ acyl group thatmay have a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent; R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ at alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent].
 2. A pharmaceutical composition according to claim 1,wherein R¹ is C₁₋₆ alkyl group (where, R¹ may have a substituentselected from 3-10-membered nonaromatic heterocyclic group that may haveC₁₋₆ alkyl group, hydroxyl group, C₁₋₆ alkoxy group, amino group,mono-C₁₋₆ alkylamino group and di-C₁₋₆ alkylamino group).
 3. Apharmaceutical composition according to claim 1, wherein R¹ is methylgroup or group represented any one of the following Formulae:

(wherein, R^(a3) represents methyl group; R^(a1) represents a hydrogenatom or hydroxyl group; R^(a2) represents methoxy group, ethoxy group,1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group,dimethylamino group or diethylamino group).
 4. A pharmaceuticalcomposition according to claim 1, wherein R¹ is methyl group or2-methoxyethyl group.
 5. A pharmaceutical composition according to claim1, wherein R² represents cyano group or group represented by Formula—CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, C₁₋₆alkyl group that may have a substituent, C₂₋₆ alkenyl group that mayhave a substituent, C₂₋₆ alkynyl group that may have a substituent, C₃₋₈cycloalkyl group that may have a substituent, C₆₋₁₀ aryl group that mayhave a substituent, 5-10-membered heteroaryl group that may have asubstituent or 3-10-membered nonaromatic heterocylic group that may havea substituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent).
 6. Apharmaceutical composition according to claim 1, wherein R² is cyanogroup or group represented by Formula —CONHV^(a16) (wherein, V^(a16)represents a hydrogen atom, C₁₋₆ alkyl group, C₃₋₈ cycloalkyl group,C₁₋₆ alkoxy group or C₃₋₈ cycloalkoxy group, where V^(a16) may have asubstituent selected from a halogen atom, cyano group, hydroxyl groupand C₁₋₆ alkoxy group).
 7. A pharmaceutical composition according toclaim 1, wherein R² is group represented by Formula —CONHV^(a17)(wherein, V^(a17) represents a hydrogen atom, C₁₋₆ alkyl group or C₁₋₆alkoxy group).
 8. A pharmaceutical composition according to claim 1,wherein R² is group represented by Formula —CONHV^(a18) (wherein,V^(a18) represents a hydrogen atom, methyl group or methoxy group).
 9. Apharmaceutical composition according to claim 1, wherein Y¹ is grouprepresented by Formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).
 10. Apharmaceutical composition according to claim 1, wherein R³ and R⁴ is ahydrogen atom.
 11. A pharmaceutical composition according to claim 1,wherein R⁵ is a hydrogen atom, C₁₋₆ alkyl group, C₃₋₈ cycloalkyl groupor C₆₋₁₀ aryl group (where, R⁵ may have a substituent selected from ahalogen atom and methanesulfonyl group).
 12. A pharmaceuticalcomposition according to claim 1, wherein R⁵ is methyl group, ethylgroup or cyclopropyl group.
 13. A pharmaceutical composition accordingto claim 1, wherein the compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof is atleast one compound selected from the group consisting of:N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino7-methoxy-6-quinolinecarboxamide;N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)cabonylamino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylaminocarbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea;N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(4-(3 ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylicacid (2-cyanoethyl)amide; andN-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea,a pharmacologically acceptable salt thereof or a solvate thereof.
 14. Apharmaceutical composition according to claim 1, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof is at least one compound selected from the groupconsisting of:4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;andN6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 15. Apharmaceutical composition according to claim 1, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereof,or a solvate thereof is4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof, or a solvate thereof.
 16. Apharmaceutical composition according to claim 1, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereof,or a solvate thereof is methanesulfonate of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.17. A pharmaceutical composition according to claim 1, wherein thesubstance having a c-kit kinase-inhibiting activity is at least onecompound selected from the group consisting of: (1)4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide;(2) 3-[(2,4-dimethylpyrrole-5-yl)methylene]-2-indolinone; (3)(Z)-3-[(2,4-dimethyl-5-(2-oxo-1,2-dihydroindole-3-ylidenemethyl)-1H-pyrrole-3-yl)-propionicacid; (4)5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylicacid (2-diethylaminoethyl)amide; (5)N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea;(6) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine; (7)N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea;(8)4-[(4-fluoro-2-methylindole-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidine-1-yl)propoxy]quinazoline;(9)6-[2-(methylcarbamoyl)phenylsulfanil]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;(10)N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;(11)[6-[4-[(4-ethylpiperazine-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yl]-((R)-1-phenylethyl)amine;(12)6-(2,6-dichloro-phenyl)-2-(4-fluoro-3-methyl-phenylamino)-8-methyl8H-pyrido[2,3-d]pyrimidine-7-one;(13)6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanilphenylamino)-8H-pyrido[2,3-/d/]pyrimidine-7-one;(14)4-[6-methoxy-7-(3-piperidine-1-yl-propoxy)quinazoline-4-yl]piperazine-1-carboxylicacid(4-isopropoxyphenyl)amide; and (15)N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazine-1-yl]-2-methylpyrimidine-4-yl]amino]thiazole-5-carboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 18. Apharmaceutical composition according to claim 1, wherein the substancehaving a c-kit kinase-inhibiting activity is4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide,a pharmacologically acceptable salt thereof, or a solvate thereof.
 19. Apharmaceutical composition according to claim 1, wherein the substancehaving a c-kit kinase-inhibiting activity is an anti-c-kit kinaseantibody.
 20. A pharmaceutical composition according to claim 1, whereina pharmaceutical composition is a pharmaceutical composition for cancertreatment.
 21. A kit comprising: (a) at least one selected from thegroup consisting of a package, an instruction and an attached documentdescribing combined use of a compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof with asubstance having a c-kit kinase-inhibiting activity; and (b) apharmaceutical composition comprising a compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof:

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen, atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent); R² represents cyano group, C₁₋₆ alkoxy group that may havea substituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent); Y¹represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); W¹ and W² eachindependently represent a carbon atom or a nitrogen atom that may have asubstituent); R³ and R⁴ each independently represent a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₆ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₂₋₇ acyl group thatmay have a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent; R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent].
 22. A kit according to claim 21, wherein R¹ is C₁₋₆ alkylgroup (where, R¹ may have a substituent selected from 3-10-memberednonaromatic heterocyclic group that may have C₁₋₆ alkyl group, hydroxylgroup, C₁₋₆ alkoxy group, amino group, mono-C₁₋₆ alkylamino group anddi-C₁₋₆ alkylamino group).
 23. A kit according to claim 21, wherein R¹is methyl group or group represented by any one of the followingFormulae

(wherein, R^(a3) represents methyl group; R^(a1) represents a hydrogenatom or hydroxyl group; R^(a2) represents methoxy group, ethoxy group,1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group,dimethylamino group or diethylamino group).
 24. A kit according to claim21, wherein R¹ is methyl group or 2-methoxyethyl group.
 25. A kitaccording to claim 21, wherein R² is cyano group or group represented byFormula —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₆ alkynyl group that may have a substituentC₃₋₈ cycloalkyl group that may have a substituent, C₆₋₁₀ aryl group thatmay have a substituent, 5-10-membered heteroaryl group that may have asubstituent or 3-10-membered nonaromatic heterocyclic group that mayhave a substituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent, C₂₋₆ alkenyl group that may have asubstituent, C₂₋₆ alkynyl group that may have a substituent, C₃₋₈cycloalkyl group that may have a substituent, C₆₋₁₀ aryl group that mayhave a substituent, 5-10-membered heteroaryl group that may have asubstituent, 3-10-membered nonaromatic heterocyclic group that may havea substituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent). 26.A kit according to claim 21, wherein R² is cyano group or grouprepresented by Formula —CONHV^(a16) (wherein, V^(a16) represents ahydrogen atom, C₁₋₆ alkyl group, C₃₋₈ cycloalkyl group, C₁₋₆ alkoxygroup or C₃₋₈ cycloalkoxy group, where V^(a16) may have a substituentselected from a halogen atom, cyano group, hydroxyl group and C₁₋₆alkoxy group).
 27. A kit according to claim 21, wherein R² is grouprepresented by Formula —CONHV^(a17) (wherein, V^(a17) represents ahydrogen atom, C₁₋₆ alkyl group or C₁₋₆ alkoxy group).
 28. A kitaccording to claim 21, wherein R² is group represented by Formula—CONHV^(a18) (wherein, V^(a18) represents a hydrogen atom, methyl groupor methoxy group).
 29. A kit according to claim 21, wherein Y¹ is grouprepresented by Formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).
 30. A kitaccording to claim 21, wherein R³ and R⁴ are hydrogen atoms.
 31. A kitaccording to claim 21, wherein R⁵ is a hydrogen atom, C₁₋₆ alkyl group,C₃₋₈ cycloalkyl group or C₆₋₁₀ aryl group (where, R⁵ may have asubstituent selected from a halogen atom and methanesulfonyl group). 32.A kit according to claim 21, wherein R⁵ is methyl group, ethyl group orcyclopropyl group.
 33. A kit according to claim 21, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof is at least one compound selected from the groupconsisting of:N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)cabonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea;N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;4-(4-((cyclopropylamino)carbonyl)aminophenoxy-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylicacid (2-cyanoethyl)amide; andN-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea,a pharmacologically acceptable salt thereof, or a solvate thereof.
 34. Akit according to claim 21, wherein the compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof isat least one compound selected from the group consisting of:4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;andN6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;a pharmacologically acceptable salt thereof, or a solvate thereof.
 35. Akit according to claim 21, wherein the compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof is4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 36. Akit according to claim 21, wherein the compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof ismethanesulfonate of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.37. A kit according to claim 21, wherein the substance having a c-kitkinase-inhibiting activity is at least one compound selected from thegroup consisting of: (1)4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide;(2) 3-[(2,4-dimethylpyrrole-5-yl)methylene]-2-indolinone; (3)(Z)-3-[(2,4-dimethyl-5-(2-oxo-1,2-dihydroindole-3-ylidenemethyl)-1H-pyrrole-3-yl)-propionicacid; (4)5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylicacid (2-diethylaminoethyl)amide; (5)N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea;(6) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine; (7)N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea;(8)4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidine-1-yl)propoxy]quinazoline;(9)6-[2-(methylcarbamoyl)phenylsulfanil]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;(10)N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;(11)[6-[4-[(4-ethylpiperazine-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yl]-((R)-1-phenylethyl)amine;(12)6-(2,6-dichloro-phenyl)-2-(4-fluoro-3-methyl-phenylamino)-8-methyl8H-pyrido[2,3-d]pyrimidine-7-one;(13)6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanilphenylamino)-8H-pyrido[2,3-/d/]pyrimidine-7-one;(14)4-[6-methoxy-7-(3-piperidine-1-yl-propoxy)quinazoline-4-yl]piperazine-1-carboxylicacid(4-isopropoxyphenyl)amide; and (15)N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazine-1-yl]-2-methylpyrimidine-4-yl]amino]thiazole-5-carboxamide,a pharmacologically acceptable salt thereof, or a solvate thereof.
 38. Akit according to claim 21, wherein the substance having a c-kitkinase-inhibiting activity is4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 39. Akit according to claim 21, wherein the substance having a c-kitkinase-inhibiting activity is an anti-c-kit kinase antibody.
 40. A kitaccording to claim 21, which is a kit for cancer treatment.
 41. A kitcomprising a set of a formulation containing the compound represented byFormula (I), a pharmacologically acceptable salt thereof or a solvatethereof, and a formulation containing a substance having a c-kitkinase-inhibiting activity:

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent); R² represents cyano group, C₁₋₆ alkoxy group that may havea substituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent); Y¹represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ allyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); W¹ and W² eachindependently represent a carbon atom or a nitrogen atom that may have asubstituent); R³ and R⁴ each independently represent a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₆ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₂₋₇ acyl group thatmay have a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent; R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent;3-10-membered nonaromatic heterocyclic group that may have asubstituent].
 42. A kit according to claim 41, wherein R¹ is C₁₋₆ alkylgroup (where, R¹ may have a substituent selected from 3-10-memberednonaromatic heterocyclic group that may have C₁₋₆ alkyl group, hydroxylgroup, C₁₋₆ alkoxy group, amino group, mono-C₁₋₆ alkylamino group anddi-C₁₋₆ alkylamino group).
 43. A kit according to claim 41, wherein R¹is methyl group or group represented by any of the following Formulae

(wherein, R^(a3) represents methyl group; R^(a1) represents a hydrogenatom or hydroxyl group; R^(a2) represents methoxy group, ethoxy group,1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group,dimethylamino group or diethylamino group).
 44. A kit according to claim41, wherein R¹ is methyl group or 2-methoxyethyl group.
 45. A kitaccording to claim 41, wherein R¹ is cyano group or group represented byFormula —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₆ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₆₋₁₀ aryl group thatmay have a substituent, 5-10-membered heteroaryl group that may have asubstituent or 3-10-membered nonaromatic heterocyclic group that mayhave a substituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent, C₂₋₆ alkenyl group that may have asubstituent, C₂₋₆ alkynyl group that may have a substituent, C₃₋₈cycloalkyl group that may have a substituent, C₆₋₁₀ aryl group that mayhave a substituent, 5-10-membered heteroaryl group that may have asubstituent, 3-10-membered nonaromatic heterocyclic group that may havea substituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent). 46.A kit according to claim 41, wherein R² represents cyano group or grouprepresented by Formula —CONHV^(a16) (wherein, V^(a16) represents ahydrogen atom, C₁₋₆ alkyl group, C₃₋₈ cycloalkyl group, C₁₋₆ alkoxygroup or C₃₋₈ cycloalkoxy group, where V^(a16) may have a substituentselected from a halogen atom, cyano group, hydroxyl group and C₁₋₆alkoxy group).
 47. A kit according to claim 41, wherein R² is grouprepresented by Formula —CONHV^(a17) (wherein, V^(a17) represents ahydrogen atom, C₁₋₆ alkyl group or C₁₋₆ alkoxy group).
 48. A kitaccording to claim 41, wherein R² is group represented by Formula—CONHV^(a18) (wherein, V^(a18) represents a hydrogen atom, methyl groupor methoxy group).
 49. A kit according to claim 41, wherein Y¹ is grouprepresented by Formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).
 50. A kitaccording to claim 41, wherein R³ and R⁴ are hydrogen atoms.
 51. A kitaccording to claim 41, wherein R⁵ is a hydrogen atom, C₁₋₆ alkyl group,C₃₋₈ cycloalkyl group or C₆₋₁₀ aryl group (where R⁵ may have asubstituent selected from a halogen atom and methanesulfonyl group). 52.A kit according to claim 41, wherein R⁵ is methyl group, ethyl group orcyclopropyl group.
 53. A kit according to claim 41, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof is at least one compound selected from the groupconsisting of:N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonylamino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′cyclopropylurea;N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylicacid (2-cyanoethyl)amide; andN-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea,a pharmacologically acceptable salt thereof, or a solvate thereof.
 54. Akit according to claim 41, wherein the compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof isat least one compound selected from the group consisting of:4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;andN6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof, or a solvate thereof.
 55. Akit according to claim 41, wherein the compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof is4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof, or a solvate thereof.
 56. Akit according to claim 41, wherein the compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof ismethanesulfonate of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.57. A kit according to claim 41, wherein the substance having a c-kitkinase-inhibiting activity is at least one compound selected from thegroup consisting of: (1)4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide;(2) 3-[(2,4-dimethylpyrrole-5-yl)methylene]-2-indolinone; (3)(Z)-3-[(2,4-dimethyl-5-(2-oxo-1,2-dihydroindole-3-ylidenemethyl)-1H-pyrrole-3-yl)-propionicacid; (4)5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylicacid (2-diethylaminoethyl)amide; (5)N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea,(6) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine; (7)N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea;(8)4-[(4-fluoro-2-methylindole-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidine-1-yl)propoxy]quinazoline;(9)6-[2-(methylcarbamoyl)phenylsulfanil]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;(10)N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;(11)[6-[4-[(4-ethylpiperazine-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yl]-((R)-1-phenylethyl)amine;(12)6-(2,6-dichloro-phenyl)-2-(4-fluoro-3-methyl-phenylamino)-8-methyl8H-pyrido[2,3-d]pyrimidine-7-one;(13)6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanilphenylamino)-8H-pyrido[2,3-/d/]pyrimidine-7-one;(14)4-[6-methoxy-7-(3-piperidine-1-yl-propoxy)quinazoline-4-yl]piperazine-1-carboxylicacid(4-isopropoxyphenyl)amide; and (15)N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazine-1-yl]-2-methylpyrimidine-4-yl]amino]thiazole-5-carboxamide,a pharmacologically acceptable salt thereof, or a solvate thereof.
 58. Akit according to claim 41, wherein the substance having a c-kitkinase-inhibiting activity is4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 59. Akit according to claim 41, wherein the substance having a c-kitkinase-inhibiting activity is an anti-c-kit kinase antibody.
 60. A kitaccording to claim 41, wherein the kit is for cancer treatment.
 61. Apharmaceutical composition comprising a compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereof,which is administered simultaneously or separately to a patient with asubstance having a c-kit kinase-inhibiting activity:

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent); R² represents cyano group, C₁₋₆ alkoxy group that may havea substituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that, may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent; C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent); Y¹represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); W¹ and W² eachindependently represent a carbon atom or a nitrogen atom that may have asubstituent); R³ and R⁴ each independently represent a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₄ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₂₋₇ acyl group thatmay have a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent; R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent].
 62. A pharmaceutical composition according to claim 61,wherein R¹ is C₁₋₆ alkyl group (where R¹ may have a substituent selectedfrom 3-10-membered nonaromatic heterocyclic group that may have C₁₋₆alkyl group, hydroxyl group, C₁₋₆ alkoxy group, amino group, mono-C₁₋₆alkylamino group and di-C₁₋₆ alkylamino group).
 63. A pharmaceuticalcomposition according to claim 61, wherein R¹ is methyl group or grouprepresented by any one of the following Formulae

(wherein, R^(a3) represents methyl group; R^(a1) represents a hydrogenatom or hydroxyl group; R^(a2) represents methoxy group, ethoxy group,1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group,dimethylamino group or diethylamino group).
 64. A pharmaceuticalcomposition according to claim 61, wherein R¹ is methyl group or2-methoxyethyl group.
 65. A pharmaceutical composition according toclaim 61, wherein R² is cyano group or group represented by Formula—CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, C₁₋₆alkyl group that may have a substituent, C₂₋₆ alkenyl group that mayhave a substituent, C₂₋₆ alkynyl group that may have a substituent, C₃₋₈cycloalkyl group that may have a substituent, C₆₋₁₀ aryl group that mayhave a substituent, 5-10-membered heteroaryl group that may have asubstituent or 3-10-membered nonaromatic heterocyclic group that mayhave a substituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent, C₂₋₆ alkenyl group that may have asubstituent, C₂₋₆ alkynyl group that may have a substituent, C₃₋₈cycloalkyl group that may have a substituent, C₆₋₁₀ aryl group that mayhave a substituent, 5-10-membered heteroaryl group that may have asubstituent, 3-10-membered nonaromatic heterocyclic group that may havea substituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent). 66.A pharmaceutical composition according to claim 61, wherein R²represents cyano group or group represented by Formula —CONHV^(a16)(wherein, V^(a16) represents a hydrogen atom, C₁₋₆ alkyl group, C₃₋₈cycloalkyl group, C₁₋₆ alkoxy group or C₃₋₈ cycloalkoxy group, whereV^(a16) may have a substituent selected from a halogen atom, cyanogroup, hydroxyl group and C₁₋₆ alkoxy group).
 67. A pharmaceuticalcomposition according to claim 61, wherein R² is group represented byFormula —CONHV^(a17) (wherein, V^(a17) represents a hydrogen atom, C₁₋₆alkyl group or C₁₋₆ alkoxy group).
 68. A pharmaceutical compositionaccording to claim 61, wherein R² is group represented by Formula—CONHV^(a18) (wherein, V^(a18) represents a hydrogen atom, methyl groupor methoxy group).
 69. A pharmaceutical composition according to claim61, wherein Y¹ is group represented by Formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).
 70. Apharmaceutical composition according to claim 61, wherein R³ and R⁴ arehydrogen atoms.
 71. A pharmaceutical composition according to claim 61,wherein R⁵ is a hydrogen atom, C₁₋₆ alkyl group, C₃₋₈ cycloalkyl groupor C₆₋₁₀ aryl group (where, R⁵ may have a substituent selected from ahalogen atom and methanesulfonyl group).
 72. A pharmaceuticalcomposition according to claim 61, wherein R⁵ is methyl group, ethylgroup or cyclopropyl group.
 73. A pharmaceutical composition accordingto claim 61, wherein the compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof is atleast one compound selected from, the group consisting, of:N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)oxy)phenyl)-N′-cyclopropylurea;N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;4-(3-chloro-4-(cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N-(2-fluoro-4-((6-carbonyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea;N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)cabonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea;N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(4-(3-ethylureido)-3 fluoro-phenoxy)-7-methoxyquinoline-6-carboxylicacid (2-cyanoethyl)amide; andN-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea,a pharmacologically acceptable salt thereof or a solvate thereof.
 74. Apharmaceutical composition according to claim 61, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof is at least one compound selected from the groupconsisting of:4-(3-chloro-4-(6-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;andN6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 75. Apharmaceutical composition according to claim 61, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof is 4-(3-chloro-4(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 76. Apharmaceutical composition according to claim 61, wherein the compoundrepresented by Formula (I), a pharmacologically acceptable salt thereofor a solvate thereof is methanesulfonate of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.77. A pharmaceutical composition according to claim 61, wherein thesubstance haying a c-kit kinase-inhibiting activity is at least onecompound selected from the group consisting of: (1)4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide;(2) 3-[(2,4-dimethylpyrrole-5-yl)methylene]-2-indolinone; (3)(Z)-3-[(2,4-dimethyl-5-(2-oxo-1,2-dihydroindole-3-ylidenemethyl)-1H-pyrrole-3-yl)-propionicacid; (4)5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylicacid (2-diethylaminoethyl)amide; (5)N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea;(6) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine; (7)N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea;(8)4-[(4-fluoro-2-methylindole-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidine-1-yl)propoxy]quinazoline;(9)6-[2-(methylcarbamoyl)phenylsulfanil]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;(10)N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;(11)[6-[4-[(4-ethylpiperazine-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yl]-((R)-1-phenylethyl)amine;(12)6-(2,6-dichloro-phenyl)-2-(4-fluoro-3-methyl-phenylamino)-8-methyl8H-pyrido[2,3-d]pyrimidine-7-one;(13)6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanilphenylamino)-8H-pyrido[2,3-/d/]pyrimidine-7-one;(14)4-[6-methoxy-7-(3-piperidine-1-yl-propoxy)quinazoline-4-yl]piperazine-1-carboxylicacid(4-isopropoxyphenyl)amide; and (15)N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazine-1-yl]-2-methylpyrimidine-4-yl]amino]thiazole-5-carboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.
 78. Apharmaceutical composition according to claim 61, wherein the substancehaving a c-kit kinase-inhibiting activity is4-(4-methylpiperazine-1-ylmethyl)-N-[4-methyl-3-[4-(3-pyridyl)pyrimidine-2-ylamino]phenyl]benzenamide,a pharmacologically acceptable salt thereof, or a solvate thereof.
 79. Apharmaceutical composition according to claim 61, wherein the substancehaving a c-kit kinase-inhibiting activity is an anti-c-kit kinaseantibody.
 80. A pharmaceutical composition according to claim 61,wherein the pharmaceutical composition is a pharmaceutical compositionfor cancer treatment.
 81. A method for treating cancer comprisingadministering an effective amount of a compound represented by Formula(I), a pharmacologically acceptable salt thereof or a solvate thereofand an effective amount of a substance having a c-kit kinase-inhibitingactivity to a patient:

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent, or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent); R² represents cyano group, C₁₋₆ alkoxy group that may havea substituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (Wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent); Y¹represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group, that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); W¹ and W² eachindependently represent a carbon atom or a nitrogen atom that may have asubstituent); R³ and R⁴ each independently represent a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₆ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₂₋₇ acyl group thatmay have a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent; R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent and3-10-membered nonaromatic heterocyclic group that may have asubstituent].
 82. Use of a compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof forproducing a pharmaceutical composition in combination with a substancehaving a c-kit kinase-inhibiting activity:

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent); R² represents cyano group, C₁₋₆ alkoxy group that may havea substituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₂₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent), Y¹represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); W¹ and W² eachindependently represent a carbon atom or a nitrogen atom that may have asubstituent); R³ and R⁴ each independently represent a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₆ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₂₋₇ acyl group thatmay have a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent; R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent].
 83. A compound represented by Formula (I), apharmacologically acceptable salt thereof or a solvate thereof forproviding a pharmaceutical composition in combination with a substancehaving a c-kit kinase-inhibiting activity: Formula (I)

[wherein, R¹ represents group represented by Formula —V¹—V²—V³ (wherein,V¹ represents C₁₋₆ alkylene group that may have a substituent; V²represents a single bond, an oxygen atom, a sulfur atom, carbonyl group,sulfinyl group, sulfonyl group, group represented by Formula —CONR⁶—,group represented by Formula —SO₂NR⁶—, group represented by Formula—NR⁶SO₂—, group represented by Formula —NR⁶CO— or group represented byFormula —NR⁶— (wherein, R⁶ represents a hydrogen atom, C₁₋₆ alkyl groupthat may have a substituent or C₃₋₈ cycloalkyl group that may have asubstituent); V³ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent); R² represents cyano group, C₁₋₆ alkoxy group that may havea substituent, carboxyl group, C₂₋₇ alkoxycarbonyl group that may have asubstituent or group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, C₁₋₆ alkyl group that may have asubstituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent; V^(a12) represents a hydrogen atom, C₁₋₆ alkyl group thatmay have a substituent, C₂₋₆ alkenyl group that may have a substituent,C₁₋₆ alkynyl group that may have a substituent, C₃₋₈ cycloalkyl groupthat may have a substituent, C₆₋₁₀ aryl group that may have asubstituent, 5-10-membered heteroaryl group that may have a substituent,3-10-membered nonaromatic heterocyclic group that may have asubstituent, hydroxyl group, C₁₋₆ alkoxy group that may have asubstituent or C₃₋₈ cycloalkoxy group that may have a substituent); Y¹represents group represented by Formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, cyano group, nitro group, amino group, C₁₋₆ alkyl groupthat may have a substituent, C₃₋₈ cycloalkyl group that may have asubstituent, C₁₋₆ alkoxy group that may have a substituent, C₁₋₆alkylthio group that may have a substituent, formyl group, C₂₋₇ acylgroup that may have a substituent, C₂₋₇ alkoxycarbonyl group that mayhave a substituent or group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor C₁₋₆ alkyl group that may have a substituent); W¹ and W² eachindependently represent a carbon atom or a nitrogen atom that may have asubstituent); R³ and R⁴ each independently represent a hydrogen atom,C₁₋₆ alkyl group that may have a substituent, C₂₋₆ alkenyl group thatmay have a substituent, C₂₋₆ alkynyl group that may have a substituent,C₃₋₈ cycloalkyl group that may have a substituent, C₂₋₇ acyl group thatmay have a substituent or C₂₋₇ alkoxycarbonyl group that may have asubstituent; R⁵ represents a hydrogen atom, C₁₋₆ alkyl group that mayhave a substituent, C₂₋₆ alkenyl group that may have a substituent, C₂₋₆alkynyl group that may have a substituent, C₃₋₈ cycloalkyl group thatmay have a substituent, C₆₋₁₀ aryl group that may have a substituent,5-10-membered heteroaryl group that may have a substituent or3-10-membered nonaromatic heterocyclic group that may have asubstituent].